Effect of Age on Efficacy and Safety of Fluticasone Furoate/Vilanterol (FF/VI), Umeclidinium (UMEC), and UMEC + FF/VI in Patients with Chronic Obstructive Pulmonary Disease: Analyses of Five Randomized Clinical Trials

Nicola A Hanania,1 Scott Caveney,2 Tedi Soule,2 Lee Tombs,3 Sally Lettis,4 Courtney Crim,5,6 David M Mannino,7 Hitesh Patel,2 Isabelle H Boucot4 1Airways Clinical Research Center, Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA; 2US Medical Affairs, GlaxoSmithKline, Research Triangle Park, NC, USA; 3Precise Approach Ltd, Contingent Worker on Assignment at GlaxoSmithKline, Brentford, Middlesex, UK; 4Statistics, GlaxoSmithKline, Brentford, Middlesex, UK; 5R&D, GlaxoSmithKline, Research Triangle Park, NC, USA; 6Internal Medicine - Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 7Department of Preventive Medicine and Environmental Health, University of Kentucky, College of Public Health, Lexington, KY, USACorrespondence: Nicola A HananiaAirways Clinical Research Center, Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USAEmail hanania@bcm.eduIntroduction: Concerns have been raised about the practical use and clinical benefits of medications and inhalers in older patients with chronic obstructive pulmonary disease (COPD). Here, we report analyses according to age from five clinical trials evaluating medications administered using the ELLIPTA dry-powder inhaler (DPI).Methods: Efficacy and safety according to age groups (< 65 and ≥ 65 years) were assessed using data from five clinical trials in patients ≥ 40 years of age with symptomatic COPD. There was a mix of pre-specified and post hoc analyses of two 24-week trials with fluticasone furoate (FF)/vilanterol (VI) 100/25 μg; one 24-week trial with umeclidinium (UMEC) 62.5 μg; and two 12-week trials with UMEC 62.5 μg + FF/VI 100/25 μg. The primary endpoint was trough forced expiratory volume in 1 second (FEV1) obtained 23 and 24 hours after dosing on the last day of the study.Results: A total of 2876 patients < 65 years of age and 2148 patients ≥ 65 years of age were enrolled across all studies of whom 1333 and 1111 patients, respectively, received treatment at the doses presented. Statistically significant and clinically meaningful treatment differences in improvement from baseline in mean trough FEV1 were reported for active comparators versus placebo at study end for both < 65 and ≥ 65 years subgroups (FF/VI vs placebo: 143 mL and 111 mL; UMEC vs placebo: 110 mL and 123 mL; UMEC + FF/VI vs placebo + FF/VI: 136 mL and 105 mL; p< 0.001 for all comparisons). The incidence of adverse events reported for active treatments was similar between age groups.Conclusion: These data provide evidence to support the use of FF/VI, UMEC, or UMEC + FF/VI, all delivered via the ELLIPTA DPI, to treat older (≥ 65 years) and younger (< 65 years) patients with COPD.Keywords: COPD, elderly, ELLIPTA dry-powder inhaler, fluticasone furoate/vilanterol, multiple-inhaler triple therapy, umeclidinium